Method for Operating a Benefit Agent Delivery System Comprising Microcells Having an Electrically Eroding Sealing Layer

ABSTRACT

A benefit agent delivery system whereby benefit agents can be delivered on demand and/or a variety of different benefit agents at different concentrations can be delivered from the same system. The benefit agent delivery system includes a microcell layer comprising a plurality of microcells, wherein the microcells are filled with a carrier and a benefit agent. The microcells include an opening, wherein the opening is spanned by a sealing layer comprising a polymer and metallic material. Application of an electric field across the microcell layer and the sealing layer results in the migration of the metallic material from the sealing layer and the creation of a porous sealing layer, allowing the benefit agent to be released from the benefit agent delivery system.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of co-pending U.S. patent applicationSer. No. 16/952,433 filed on Nov. 19, 2020 (Publication No.US20210154133 A1), which claims priority to U.S. Provisional ApplicationNo. 62/941,216 filed on Nov. 27, 2019, which is incorporated herein byreference in its entirety.

BACKGROUND OF THE INVENTION

The development of methodologies for controlled and extended release ofbenefit agents have attracted significant attention during the lastdecades. This is true for a large variety of benefit agents includingpharmaceutical, nutraceutical agents, agricultural nutrients and relatedsubstances, cosmetic agents, fragrances, air care agents, and many otherbenefit agents in a variety of fields. Transdermal delivery ofpharmaceutical agents has proven effective for drugs that are able tomove across the skin barrier. For example, small amounts of nicotine canbe delivered over extended periods with transdermal patches that suspendthe nicotine in an ethylene vinyl acetate (EVA) copolymer. See, e.g.,Nicoderm-CQ® by GlaxoSmithKline (Brentford, UK). Other examples includeextended release of fragrances and malodor removing agents for improvingthe air quality in living spaces and automobiles, fertilizers in thesoil for more efficient food production, and biocides on surfaces formitigating microorganism growth. Controlled and extended releasedelivery systems may involve the delivery of various benefit agents indifferent forms, such as solid, liquid and gas, to different locations,and under different conditions.

A variety of delivery systems has been developed during the last decadesthat provide on demand delivery of benefit agents. For instance, ChronoTherapeutics (Hayward, CA) is currently testing a micro pump-enabledsmart transdermal patch for delivering nicotine. Nonetheless, thecorresponding device is large and visible through clothing as a sizeablebump. Thus, there remains a need for small, simle, inexpensive,versatile and safe delivery systems for delivering benefit agents ondemand.

SUMMARY OF THE INVENTION

The invention addresses this need by providing a low power deliverysystem whereby a benefit agent or a mixture of benefit agents can bereleased on demand. Additionally, as described below, the inventionprovides a system for delivering varying amounts of benefit agents fromthe same delivery system at different times, and for delivering multiplebenefit agents at the same or different times from the same benefitagent delivery system.

In one aspect, the invention is a benefit agent delivery systemcomprising a conductive layer, a microcell layer comprising a pluralityof microcells, wherein each microcell includes an opening, a sealinglayer spanning the opening of each microcell, and an electrode layer. Amedium, comprising a carrier and a benefit agent, is contained in theplurality of microcells.

The sealing layer comprises a polymeric material and a metallicmaterial. The conductive layer, the microcell layer, the sealing layer,and the electrode layer are vertically stacked on each other. Theconductive layer, the microcell layer, the sealing layer and theelectrode layer may be vertically stacked upon each other in this order.The plurality of microcells and the sealing layer are disposed betweenthe conductive layer and the electrode layer. The benefit agent deliverysystem may further comprise a voltage source that is coupled to theconductive layer and the electrode layer. When a voltage is applied fromthe voltage source coupled to the conductive layer and the electrodelayer, the resulting electric current may flow through the medium. Whena voltage is applied from a voltage source coupled to the conductivelayer and the electrode layer, the metallic material is removed from thesealing layer, creating a porous sealing layer. The electrode layer maybe porous.

In one embodiment, the polymeric material of the sealing layer maycomprise an acrylate, a methacrylate, a polycarbonate, a polyvinylalcohol, cellulose, poly(N-isopropylacrylamide) (PNIPAAm),poly(lactic-co-glycolic acid) (PLGA), polyvinylidene chloride,acrylonitrile, amorphous nylon, oriented polyester, terephthalate,polyvinyl chloride, polyethylene, polypropylene, polyurethane, alginate,and polystyrene. The metallic material of the sealing layer may be metalparticles, metal wires, metal fibers, metal flakes, metal rods, metalaggregates, or metal disks. The smallest dimension of the metalparticles, metal wires, metal fibers, metal rods, and metal aggregatesmay be from about 1 μm to about 100 μm. The metal flakes and metal disksmay have average thickness of from about 1 nm to about 200 nm, andaverage diameter of from 100 nm to about 500 μm. The metallic materialof the sealing layer may also be metal nanoparticles, metal nanowires,metal nanofibers or combinations thereof. The smallest dimension of themetal nanoparticles, metal nanowires, and metal nanofibers may be fromabout 20 nm to about 1 μm. The metallic material of the sealing layermay comprise metal elements such as silver, copper, platinum, gold,zinc, nickel, chromium or combinations thereof.

In one embodiment, the microcells may comprise a variety of benefitagents. The benefit agent may be a pharmaceutical agent, a vaccine, anantibody, a hormone, a protein, a nucleic acid, a nutraceutical agent, anutrient, a cosmetic agent, a fragrance, a malodor removing agent, anagricultural agent, an air care agent, a preservative, an anti-microbialagent and other benefit agents.

In one embodiment, the benefit agent may be dissolved or dispersed inthe carrier. The carrier may be water, an organic compound, a siliconecompound, or combinations thereof. The organic compound may be analcohol, an ester, an amide, an ether, a carboxylic acid, a hydrocarbonor other organic compound. The organic compound may be an organicsolvent, such as DMSO, ethylene glycol, polyethylene glycol, propyleneglycol, dipropylene glycol, glycerin, octane, nonane, triethyl citrate,ethylene carbonate, or dimethyl carbonate.

The medium that is included in the plurality of microcells may comprisemore than 0.01 weight %, or more than 0.1 weight %, or more than 1weight % of the benefit agent by weight of the medium. The medium maycomprise from 0.001 weight % to 99.99 weight %, or from 0.01 weight % to99 weight %, or from 0.1 weight % to 95 weight %, or form 5 weight % to60 weight % of the benefit agent by weight of the medium.

In another embodiment of the benefit agent delivery system, a microcellmay contain a benefit agent or a mixture of benefit agents. Because theinvention includes a plurality of microcells, it is possible to havedifferent microcells within the same benefit delivery system containingdifferent combination of benefit agents or similar combinations havingdifferent concentrations. For example, a system may include firstmicrocells containing a first benefit agent and second microcellscontaining a second benefit agent, or a system may include firstmicrocells containing a benefit agent at a first concentration andsecond microcells containing the same benefit agent at a secondconcentration. In other embodiments, the system may include firstmicrocells containing a benefit agent and second microcells containingan adjuvant. Other combinations of benefit agents, additives, andconcentrations will be evident to one of skill in the art.

In another aspect, the invention is a method of operation a benefitagent delivery system comprising the steps of (1) providing a benefitagent delivery system comprising (a) a conductive layer, (b) a microcelllayer comprising a plurality of microcells, wherein each microcellincludes an opening and contains a carrier and a benefit agent, (c) asealing layer spanning the opening of each microcell and comprising apolymeric material and a metallic material, (d) an electrode layer; and(e) a voltage source; the conductive layer, the microcell layer, thesealing layer and the electrode layer are vertically stacked upon eachother; the microcell layer and the sealing layer are disposed betweenthe conductive layer and the electrode layer; the voltage source iscoupled to the conductive layer and the electrode layer; (2) applying avoltage potential difference between the conductive layer and theelectrode layer to generate an electric field having a polarity causingthe migration of the metallic material onto a surface of the microcelladjacent to the conductive layer. When the voltage is applied, theresulting electric current flows through the medium. The rate ofdelivery of the benefit agent may be controlled by the selection of theapplied voltage potential

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1A illustrates an embodiment of a benefit agent delivery systemincluding a conductive layer, a plurality of microcells comprising abenefit agent, a sealing layer with a metallic material, and anelectrode layer;

FIG. 1B illustrates an embodiment of a benefit agent delivery systemincluding a continuous conductive layer, a plurality of microcellscomprising a benefit agent, a porous sealing layer, and a voltagesource. In the system depicted in FIG. 1B, the benefit agent may passthrough the porous sealing layer of one of the microcells to bedelivered where desired;

FIG. 2 illustrates another embodiment of a benefit agent delivery systemincluding an conductive layer, a plurality of microcells comprising abenefit agent, a sealing layer with a metallic material, and acontinuous electrode layer.

FIGS. 3A and 3B illustrates a potential mechanism for the migration themetallic material of the sealing layer;

FIG. 4 illustrates a benefit agent delivery system including a pluralityof different types of benefit agents and/or a plurality ofconcentrations of benefit agents in the same delivery system;

FIG. 5 shows a method for making microcells for the invention using aroll-to-roll process;

FIGS. 6A and 6B detail the production of microcells for an activemolecule delivery system using photolithographic exposure through aphotomask of a conductor film coated with a thermoset precursor;

FIGS. 6C and 6D detail an alternate embodiment in which microcells for abenefit agent delivery system are fabricated using photolithography. InFIGS. 6C and 6D a combination of top and bottom exposure is used,allowing the walls in one lateral direction to be cured by top photomaskexposure, and the walls in another lateral direction to be cured bottomexposure through the opaque base conductor film. This process allowsmicrocell walls to be prepared with varying porosity for use withlateral motion embodiments;

FIGS. 7A-7D illustrate the steps of filling and sealing an array ofmicrocells to be used in a benefit agent delivery system;

FIG. 8 illustrates an embodiment of a benefit agent delivery systemincluding a plurality of microcells and a sealing layer comprisingmetallic material, which can be activated by applied electric field. Themicrocell is activated by an electrode while the conductivity of theskin (or other conductive substrate) provides a grounding electrode;

FIG. 9 illustrates an embodiment of a benefit agent delivery systemincluding a plurality of microcells and a sealing layer comprisingmetallic material. In FIG. 9 a switch is coupled to a wireless receiverallowing a user to activate a microcell to trigger the delivery of thebenefit agent with an application on a mobile phone or other wirelessdevice;

FIG. 10 illustrates an embodiment of a benefit agent delivery systemincluding a plurality of microcells and a sealing layer comprisingmetallic material. In FIG. 10 , a plurality of electrodes is coupled toa matrix driver that is coupled to a wireless receiver, thereby allowingan application to activate the delivery of the desired benefit agent;

FIGS. 11 and 12 illustrate an embodiment of a benefit agent deliverysystem wherein the benefit agents are not only loaded into themicrocells, but also in other layers such as an adhesive layer and/or abenefit agent loading layer. Different combinations of benefit agentscan be included in different areas of the delivery system;

FIG. 13 is a microscopic image of the outside surface of a sealing layerof a benefit agent delivery system. The sealing layer comprises metalnanofibers;

FIG. 14A is a photographic image of the outside surface of a pluralityof microcells of a benefit delivery system before application ofelectrical field across the system; the image represents the outsidesurface of the plurality of the microcells opposite from the sealinglayer;

FIG. 14B is a photographic image of the outside surface of a pluralityof microcells of a benefit delivery system after application ofelectrical field across the system; the image represents the outsidesurface of the plurality of the microcells opposite from the sealinglayer; the electrical field is applied on the left side of the benefitagent delivery system; no electrical field was applied at the rightside;

FIG. 15A is a microscopic image of the inside surface of a plurality ofmicrocells of a benefit delivery system before application of electricalfield across the system; the image was acquired after the removal of thesealing layer;

FIG. 15B is a microscopic image of the inside surface of a plurality ofmicrocells of a benefit delivery system after application of electricalfield across the system; the image was acquired after the removal of thesealing layer.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides a benefit agent delivery system whereby benefitagents can be released on demand and/or a variety of different benefitagents can be delivered from the same system and/or differentconcentrations of benefit agents can be delivered from the same system.The invention can be used to deliver a pharmaceutical agent, a vaccine,an antibody, a hormone, a protein, a nucleic acid, a nutrient, anutraceutical agent, a cosmetic agent, a fragrance, a malodor removingagent, an air care agent, an agricultural agent, an air care agent, ananti-microbial agent, a preservative, and other benefit agents.Pharmaceutical agents and cosmetic agents may be delivered to patientstransdermally. However, the invention may be used to deliver benefitagents to animals, generally. For example, the invention can delivertranquilizing agents to a horse during transport. In addition, theinvention may be used to deliver benefit agents to other surfaces orspaces.

“Adhesive layer” of the benefit agent delivery system is a layer thatestablishes an adhesive connection between two other layers of thesystem. An adhesive layer may have thickness of from 200 nm to 5 mm, orfrom 1 μm to 100 μm.

“Porous diffusion layer” is a layer of the benefit agent delivery systemthat has average pore size that is larger than 0.2 nm. “Rate controllayer” is a layer of the benefit agent delivery system that has averagepore size that is 0.2 nm or smaller.

In one embodiment of the present invention, the benefit agent deliverysystem includes a conductive layer, a microcell layer, a sealing layer,and an electrode layer. The conductive layer, the microcell layer, thesealing layer, and the electrode layer are vertically stacked upon eachother. In a preferred embodiment, the conductive layer, the microcelllayer, the sealing layer, and the electrode layer are vertically stackedupon each other in this order. The benefit agent delivery system mayalso comprise a voltage source connecting the conductive layer with theelectrode layer.

The microcell layer comprises a plurality of microcells containing amedium. Each of the plurality of microcells may have a volume greaterthan 0.01 nL, greater than 0.05 nL, greater than 0.1 nL, greater than 1nL, greater than 10 nL, or greater than 100 nL. The medium, which is abenefit agent formulation, comprises a carrier and a benefit agent. Themedium may comprise more than 0.01 weight %, or more than 0.1 weight %,or more than 1 weight % of the benefit agent by weight of the medium.The medium may comprise from 0.001 weight % to 99.99 weight %, or from0.01 weight % to 99 weight %, or from 0.1 weight % to 95 weight %, orform 5 weight % to 60 weight % of the benefit agent by weight of themedium.

The carrier may be a liquid, a semi-solid, a gel, such as a hydrogel, orcombinations thereof. The carrier may comprise water, an organiccompound, a silicone compound or combinations thereof. The organiccompound may be an alcohol, an ester, an amide, an ether, a carboxylicacid, a hydrocarbon and other organic compounds. The organic compoundmay be an organic solvent such as DMSO, ethylene glycol, polyethyleneglycol, propylene glycol, dipropylene glycol, glycerin, octane, nonane,triethyl citrate, ethylene carbonate, dimethyl carbonate and otherorganic solvents. The organic compound may be a biocompatible non-polarliquid. The organic compound may be a natural oil, such as vegetableoil, fruit oil, or nut oil. The silicone compound may be a silicone oil.In other embodiments, the carrier may be an aqueous liquid, such aswater or an aqueous buffer. The content of carrier in the medium may befrom about 1 weight % to about 99 weight %, preferably from about 5weight % to about 95 weight %, more preferably from about 10 weight % toabout 90 weight % by weight of the medium. The medium may also comprisea polymeric material. In one example, a benefit agent may be dispersedin the polymeric material before it is added into the microcells.

The medium may also comprise additives, such as charge control agents,rheology modifiers, and chelants. A charge control agent is typically amolecule comprising ionic or other polar groups, such as, for example,positive or negative ionic groups, which are preferably attached to anon-polar chain (typically a hydrocarbon chain). Rheology modifiers arecompounds, typically polymeric materials, which adjust the viscosity ofthe medium to the desired value. A chelant is a compound, which is ableto chelate metal cations. The presence of the chelant may facilitate themigration of the metallic material from the sealing layer. Non-limitingexample of chelants include ethylenediaminetetraacetic acid (EDTA),ethylene diamine di succinic acid (EDDS), aminotri(methylenephosphonicacid) (ATMP), 1,3-diamino-2-propanoltetraacetic acid (DTPA), dipicolinicacid (DPA), and ethylenediamine-N,N′-bis(2-hydroxyphenylacetic acid)(EDDHA). The medium may contain from 0.001 weight % to 5 weight or from0.01 weight % to 3 weight or from 0.1 weight to 1 weight % of a chelantby weight of the medium.

The microcells include an opening. The largest dimension of themicrocell opening may be from 30 μm to 300 μm, or from 30 μm to 180 μm,or from about 80 μm to 150 μm. A sealing layer spans the opening of eachmicrocell. The sealing layer comprises a polymeric material and ametallic material. The metallic material may comprise metal particles,metal wires, metal fibers, metal flakes, metal rods, metal aggregates,metal disks, and combinations thereof. The metallic material maycomprise metal nanoparticles, metal nanowires, metal nanofibers, andcombinations thereof. The metallic material may be present in thesealing layer as a metal-coated silica particles, metal-coatedsemiconductor particles, metal-coated glass beads, or metal-coatedplastic beads. The metallic material of the sealing layer may comprisemetal elements such as silver, copper, platinum, gold, zinc, nickel,chromium or combinations thereof. The sealing layer may also comprise aconductive material such as carbon black, carbon nanotubes, graphene ora conductive polymer. The smallest dimension of the metallic materialmay be from 1 nm to 1 mm, or from 20 nm to 500 μm, or from 30 nm to 100μm. In the cases of metal wires, metal fibers, metal rods, and metalaggregates, the smallest dimension may be from 1 μm to 100 μm, or from 2μm to 50 μm, or from 5 μm to 20 μm. The metal flakes and metal disks mayhave average thickness of from 1 nm to 200 nm, or from 5 nm to 100 nm,and average diameter of from 100 nm to 500 nm, or from 150 nm to 300 nm.The metallic material of the sealing layer may be in the form of metalnanoparticles, metal nanowires, and metal nanofibers. In these cases,the smallest dimension of the nanostructures may be from 20 nm to 1 μm,or from 50 nm to 500 nm, or from 75 nm to 250 nm. The content of themetallic material may be from about 1 weight % to about 90 weight %,preferably from about 3 weight % to about 70 weight %, more preferablyfrom about 5 weight % to about 40 weight % by weight of the notactivated sealing layer. The sealing layer may have thickness of from500 nm to 3 mm, or from 1 μm to 100 μm.

The plurality of the microcells and the sealing layer are disposedbetween the conductive layer and the electrode layer. The electrodelayer may comprise a single electrode. The electrode layer may be a meshfrom a metallic material having rows and columns. The electrode layermay also comprise a plurality of electrodes (also called pixelelectrodes), which may be independently addressed. The average largestdimension of the pixel electrodes may be from about 4 μm to about 4 mm,preferably from about 10 μm to about 500 μm, more preferably from about50 to about 200 μm. The electrode layer may also comprise a continuousconductive material. The continuous conductive material may be apre-formed conductor film, such as indium tin oxide (ITO) conductorlines. Other conductive materials, such as silver or aluminum, may alsobe used. The thickness of the electrode layer may be from 500 nm to 5mm, or from 1 μm to 500 μm. In the case of the continuous conductivematerial, such as ITO, the thickness of the electrode layer may be from0.1 nm to 1 μm, or from 1 nm to 100 nm. The electrode layer may beporous, having average pore size larger than 0.2 nm, or larger than 10nm, or larger than 100 nm, or larger than 1 μm, or larger than 10 um, orlarger than 100 μm. The electrode layer may also have average pore sizeless than 0.2 nm. In general, the smaller the average pore size, thelower the rate of delivery of the benefit agent from the deliverysystem.

The conductive layer may comprise a continuous conductive material. Thecontinuous conductive material may be a pre-formed conductor film, suchas indium tin oxide (ITO) conductor lines. Other conductive materials,such as silver or aluminum, may also be used. In this case, thethickness of the electrode layer may be from 0.1 nm to 1 μm, or from 1nm to 100 nm. The conductive layer may also comprise a mesh of ametallic material having rows and columns. It may also comprise aplurality of electrodes, such as pixel electrodes, which may beindependently addressed. In these cases, the thickness of the conductivelayer may be from 500 nm to 5 mm, or from 1 μm to 500 um.

The benefit agent delivery system comprises a plurality of microcellshaving a sealing layer that is initially impermeable (or has lowpermeability) to the benefit agent as depicted in FIG. 1A. Uponapplication of a voltage between the conductive layer and an electrodeof the electrode layer, the metallic material of the sealing layer isremoved from the sealing layer. It may migrate through the microcell anddeposited onto the inside surface of the microcell adjacent to theconductive layer. The applied voltage may be from about 1 to about 240V, preferably from about 5 to about 130 V, more preferably from about 20to about 80 V. The duration of the application of the voltage may befrom about 1 second to about 120 minute, preferably from about 10seconds to about 60 minutes, more preferably from about 1 minute toabout 30 minutes. When a voltage is applied from a voltage sourcebetween the conductive layer and the electrode layer, the resultingelectric current may flow through the medium. It is likely that themetallic material of the sealing layer is oxidized to the correspondingmetal salt near the anode with the application of the electric field.The metal salt may be dissolved into the medium in the microcell andthen it may be reduced near the cathode into its metal form anddeposited on the inside surface of the microcell adjacent to theconductive layer. The process creates porosity in the sealing layer asdepicted in FIG. 1B, activating the microcell. As a result, the benefitagent of the microcell may exit the corresponding microcell from thesurface adjacent to the sealing layer, as the arrow of FIG. 1B shows, tobe delivered on the desired surface or space. The porosity of thesealing layer of the activated microcell may be from about 0.01% toabout 80%, preferably from about 0.5% to about 50%, more preferably fromabout 1% to about 20% determined as total volume of pores per totalvolume of the corresponding sealing layer. The polarity of the voltagethat triggers the migration of the metal and the activation of themicrocell is such that the electrode of the electrode layer has apositive potential (anode). The ability to create porosity in thesealing layer by the application of a voltage enables the delivery ofthe benefit agent on demand. Because the benefit agent delivery systemmay comprise a plurality of microcells that can be independentlyactivated on demand, the system has the flexibility of deliveringvariable quantities of benefit agents at different times. Additionally,the microcell arrays may be loaded with different benefit agents,thereby providing a mechanism to deliver different or complimentarybenefit agents on demand.

In addition to more conventional applications, such as transdermaldelivery of pharmaceutical compounds, the benefit agent delivery systemmay be the basis for delivering agricultural nutrients. The microcellarrays can be fabricated in large sheets that can be used in conjunctionwith hydroponic growing systems, or they can be integrated into hydrogelfilm farming, such as demonstrated by Mebiol, Inc. (Kanagawa, Japan).The benefit agent delivery system can be incorporated into thestructural walls of smart packing, as well. The delivery system, forexample, makes it possible to have long-term release of antioxidantsinto a package containing fresh vegetables or other items. Suchpackaging could dramatically improve the shelf life of certain foods andother items yet will only require the amount of antioxidant necessary tomaintain freshness until the package is opened.

An overview of a benefit agent delivery system is shown in FIG. 1A. Thesystem includes a microcell layer comprising a plurality of microcells(130A, 130B, 130C), each microcell including a medium (a benefit agentformulation), that comprises a carrier 140 and a benefit agent 150. Evenif FIG. 1A (and also FIGS. 1B, 2, 3, 7, 8, 9, 10, 11, and 12 )represents the benefit agent 150 as a separate macroscopic entity, whichmay imply a different phase than the carrier, this representation shouldbe assumed to include the option of the benefit agent existing in amolecular state in the form of solution in the carrier or in any otherform, wherein the presence of the benefit agent is not apparentlyvisible as a separate phase. Such examples include microemulsions,nanoemulsions, colloidal dispersions, etc. Each microcell is part of anarray that is formed from a polymer matrix, which is described in moredetail below. The benefit agent delivery system will typically include abacking layer 110 to provide structural support and protection againstmoisture ingress and physical interactions. The backing layer may havethickness of from 1 μm to 5 mm, or from 25 μm to 300 μm. A portion ofthe microcells will have an opening that is spanned by a sealing layer160. The sealing layer may be constructed from a variety of natural ornon-natural polymers, such as comprises acrylates, methacrylates,polycarbonates, polyvinyl alcohols, cellulose,poly(N-isopropylacrylamide) (PNIPAAm), poly(lactic-co-glycolic acid)(PLGA), polyvinylidene chloride, acrylonitrile, amorphous nylon,oriented polyester, terephthalate, polyvinyl chloride, polyethylene,polypropylene, polystyrene, polyurethane or alginate. The sealing layeralso comprises a metallic material in the form of metal particles, metalwires, metal fibers, metal flakes, metal rods, metal aggregates, metaldisks, or combinations thereof. The sealing layer may comprise metallicmaterial in the form of nanoparticles, metal nanowires or metalnanofibers (170). The sealing layer may also comprise additionalconductive materials such as carbon black, carbon nanotubes, graphene ora conductive polymer. Non-limiting examples of conductive polymers thatcan be used in the sealing layer include PEDOT-PSS, polyacetylene,polyphenylene sulfide, polyphenylene vinylene, or combinations thereof.The sealing layer may also comprise a benefit agent, which is the sameor different that a benefit agent included in the medium of themicrocells. The benefit agent may be incorporated in the sealing layerwhen the sealing layer composition is prepared and before the sealinglayer is used during the preparation of the benefit agent deliverysystem. The horizontal cross section of the microcells may havedifferent shapes, for example, square, round, or polygonal, such as ahoneycomb structure.

The plurality of microcells (130A, 130B, 130C) and the sealing layer 160are disposed between a conductive layer 120 and an electrode layer 190.The electrode layer 190 may be a mesh from a metallic material havingrows and columns. The electrode layer may also comprise or a pluralityof electrodes. The electrode layer may comprise a plurality ofelectrodes 195. Often the system will additionally include an adhesivelayer 180. The electrode layer and the sealing layer may be integratedinto one layer. In FIG. 1A, the adhesive layer is between the sealinglayer and the electrode layer. The adhesive layer and the electrodelayer may be porous to the benefit agent. The adhesive layer may havethickness of from 200 nm to 5 mm, or from 1 μm to 100 μm.

FIG. 1B shows an example of a benefit agent delivery system after theactivation of a microcell. As described above, the activation takesplace via the application of a voltage 210 across the microcell, leadingto the migration of the metallic material 170. The migration of themetallic material 170 creates a layer having open channels 175. Thus,the sealing layer adjacent to the activated microcell become porous.More specifically, in FIG. 1B the sealing layer portion that spans theopening of the leftmost microcell 130A is porous, because the initiallypresent metallic material 170 has migrated, creating open channels 175.This migration results in the deposition of the metallic material 178 onthe surface of microcell 130A adjacent to the conductive layer 120. Asshown in FIG. 1B, the benefit agent that is present in microcell 130A,may exit the microcell through the now porous sealing layer (as thearrow indicates) and can be delivered on a desired surface or space. Therate of delivery of the benefit agent can be controlled by a variety ofways. Examples include the content of the metallic material in thesealing layer and the size of the smallest dimension of the metallicmaterial, which is dispersed in the sealing layer. These parametersaffect the porosity of the sealing layer. Typically, the larger thecontent of the metallic material in the sealing layer and the larger thesmallest dimension of the metal material is, the more porous the sealinglayer will be and the higher the rate of delivery. Other parameters thatmay affect the rate of delivery include the nature of the benefit agentand the carrier and the concentration of the benefit agent in thecarrier composition. The inclusion of a rate control layer in thebenefit agent delivery system may also control the rate of delivery, asdescribed in more detail below. The benefit agent may be present in themicrocell in a molecular form, that is, as a solution in the carrierand/or as an entity in a different phase as a dispersion or an emulsion.In the latter case (different phase), the particle or droplet size ofthe dispersion or emulsion will also affect the rate of delivery. Theduration of the delivery of the benefit agent can be also controlled bythe magnitude of the applied voltage, which will affect the rate of themigration of the metallic material of the sealing layer and the rate ofthe creation of the porosity in the sealing layer. Application of highervoltage typically results in higher rate of delivery of the benefitagent. The useful physical form of the benefit agent may be gaseous,independently of the actual physical form exiting the benefit agentdelivery system. For example, fragrance molecules vaporize to reach thenasal odor sensors of the user before they are detected. Thus, this kindof benefit agents may exit the delivery system as a liquid or as a gas.

The activation of a microcell is achieved by an applied voltage betweenthe conductive layer 120 and the corresponding electrode 195, asillustrated in FIGS. 3A and 3B. The application of the voltage resultsin an electric current, which flows through the medium of the microcell.In the embodiment illustrated in FIGS. 3A and 3B, the sealing layer 160of the microcell comprises a polymeric material wherein silvernanofibers 170 are dispersed, as illustrated in FIG. 3A. The appliedvoltage 210 is such that the electrode 195 has positive polarity. Thesilver nanofibers of the sealing layer migrate and are redeposited ontothe inside surface of the microcell (178). It is likely that this is theresults of oxidization of the silver nanofibers to silver saltscomprising silver cation (Ag+), which may dissolve in the medium of themicrocell and may move towards the conductive layer 120. The electronsgenerated from the metallic material oxidation may also move towards theconductive layer 120 via the electrical coupling between the conductivelayer 120 and the electrode 195. In FIG. 3B, the result of this processis illustrated. The silver cations may be reduced to silver metal on theinside surface of the microcell adjacent to the conductive layer by thetransferred electrons. The metallic silver is then deposited on theinside surface of the microcell (178). The migration of the silvernanofibers 170 from the sealing layer creates open channels 175 on thesealing layer 160, activating the microcell and enabling the delivery ofthe benefit agent, which is present in the microcell.

In addition to regulating the rate of delivery of benefit agent, themicrocell construction of the invention lends itself to making arrays ofdiffering benefit agents, or arrays of different concentrations, asillustrated in FIG. 4 . Because the microcells can be individuallyactivated with an active matrix of electrodes, it is possible to providevarying benefit agents on demand and to produce complex dosing profiles.Using injection with inkjet or other fluidic systems, individualmicrocells can be filled to enable a variety of different benefit agentsto be included in a benefit agent delivery system. For example, a systemof the invention may include nicotine at four different concentrations,thereby allowing different dosages to be delivered at different timesduring the day. For example, shortly after waking up the mostconcentrated dose may be delivered (dark gray), followed by a much lowertaper dose during the day (speckled), until the time that a user needsanother more concentrated dose. It is possible to include differentbenefit agents in the same microcell. For example, the systemillustrated in FIG. 4 may also include an analgesic (stripes) to reduceswelling and itching in the area of the skin that is in contact with thedelivery system. Of course, a variety of combinations are possible, andvarying microcells might include pharmaceuticals, nutraceuticals,nutrients, adjuvants, vitamins, vaccines, hormones, cosmetic agents,fragrances, preservatives, etc. Furthermore, the arrangement of themicrocells may not be distributed. Rather, the microcells may be filledin clusters, which makes filling and activation more straightforward. Inother embodiments, smaller microcell arrays may be filled with the samemedium, i.e., having the same benefit agent at the same concentration,and then the smaller arrays assembled into a larger array to make adelivery system of the invention.

In another embodiment illustrated by FIG. 2 , the benefit agent deliverysystem includes a conductive layer 290, a microcell layer comprising aplurality of electrodes (130A 130B, 130C), a sealing layer 160comprising a metallic material 170, and an electrode layer 220. Theconductive layer 290, the microcell layer, the sealing layer 160, andthe electrode layer 220 are vertically stacked upon each other. In thisembodiment, the conductive layer 290 may comprises multiple electrodes295 (such as pixel electrodes), or it may comprise a mesh from ametallic material having rows and columns. The benefit agent deliverysystem may also comprise a backing layer 211 as well as a voltage sourcethat connects the electrode layer with the porous conductive layer (notshown in FIG. 2 ). The plurality of microcells comprise a benefit agent150. In this embodiment, the electrode layer may be a continuousconductive material (such as ITO). The electrode layer and the sealinglayer may be integrated in one layer.

Techniques for constructing microcells. Microcells may be formed eitherin a batchwise process or in a continuous roll-to-roll process asdisclosed in U.S. Pat. No. 6,933,098. The latter offers a continuous,low cost, high throughput manufacturing technology for production ofcompartments for use in a variety of applications including benefitagent delivery and electrophoretic displays. Microcell arrays suitablefor use with the invention can be created with microembossing, asillustrated in FIG. 5 . A male mold 500 may be placed either above theweb 504 or below the web 504 (not shown); however, alternativearrangements are possible. For examples, please see U.S. Pat. No.7,715,088, which is incorporated herein by reference in its entirety. Aconductive substrate may be constructed by forming a conductor film 501on polymer substrate that becomes the backing for a device. Acomposition comprising a thermoplastic, thermoset, or a precursorthereof 502 is then coated on the conductor film. The thermoplastic orthermoset precursor layer is embossed at a temperature higher than theglass transition temperature of the thermoplastics or thermosetprecursor layer by the male mold in the form of a roller, plate or belt.

The thermoplastic or thermoset precursor for the preparation of themicrocells may be multifunctional acrylate or methacrylate, vinyl ether,epoxide and oligomers or polymers thereof, and the like. A combinationof multifunctional epoxide and multifunctional acrylate is also veryuseful to achieve desirable physico-mechanical properties. Acrosslinkable oligomer imparting flexibility, such as urethane acrylateor polyester acrylate, may be added to improve the flexure resistance ofthe embossed microcells. The composition may contain polymer, oligomer,monomer and additives or only oligomer, monomer and additives. The glasstransition temperatures (or T_(g)) for this class of materials usuallyrange from about −70° C. to about 150° C., preferably from about −20° C.to about 50° C. The microembossing process is typically carried out at atemperature higher than the T_(g). A heated male mold or a heatedhousing substrate against which the mold presses may be used to controlthe microembossing temperature and pressure.

As shown in FIG. 5 , the mold is released during or after the precursorlayer is hardened to reveal an array of microcells 503. The hardening ofthe precursor layer may be accomplished by cooling, solvent evaporation,cross-linking by radiation, heat or moisture. If the curing of thethermoset precursor is accomplished by UV radiation, UV may radiate ontothe transparent conductor film from the bottom or the top of the web asshown in the two figures. Alternatively, UV lamps may be placed insidethe mold. In this case, the mold must be transparent to allow the UVlight to radiate through the pre-patterned male mold on to the thermosetprecursor layer. A male mold may be prepared by any appropriate method,such as a diamond turn process or a photoresist process followed byeither etching or electroplating. A master template for the male moldmay be manufactured by any appropriate method, such as electroplating.With electroplating, a glass base is sputtered with a thin layer(typically 3000 Å) of a seed metal such as chrome inconel. The mold isthen coated with a layer of photoresist and exposed to UV. A mask isplaced between the UV and the layer of photoresist. The exposed areas ofthe photoresist become hardened. The unexposed areas are then removed bywashing them with an appropriate solvent. The remaining hardenedphotoresist is dried and sputtered again with a thin layer of seedmetal. The master is then ready for electroforming. A typical materialused for electroforming is nickel cobalt. Alternatively, the master canbe made of nickel by electroforming or electroless nickel deposition.The floor of the mold is typically between about 50 to 400 microns. Themaster can also be made using other microengineering techniquesincluding e-beam writing, dry etching, chemical etching, laser writingor laser interference as described in “Replication techniques formicro-optics”, SPIE Proc. Vol. 3099, pp. 76-82 (1997). Alternatively,the mold can be made by photomachining using plastics, ceramics ormetals.

Prior to applying a UV curable resin composition, the mold may betreated with a mold release to aid in the demolding process. The UVcurable resin may be degassed prior to dispensing and may optionallycontain a solvent. The solvent, if present, readily evaporates. The UVcurable resin is dispensed by any appropriate means such as, coating,dipping, pouring or the like, over the male mold. The dispenser may bemoving or stationary. A conductor film is overlaid the UV curable resin.Pressure may be applied, if necessary, to ensure proper bonding betweenthe resin and the plastic and to control the thickness of the floor ofthe microcells. The pressure may be applied using a laminating roller,vacuum molding, press device or any other like means. If the male moldis metallic and opaque, the plastic substrate is typically transparentto the actinic radiation used to cure the resin. Conversely, the malemold can be transparent and the plastic substrate can be opaque to theactinic radiation. To obtain good transfer of the molded features ontothe transfer sheet, the conductor film needs to have good adhesion tothe UV curable resin, which should have a good release property againstthe mold surface.

Microcell arrays for the invention typically include a pre-formedconductor film, such as indium tin oxide (ITO) conductor lines; however,other conductive materials, such as silver or aluminum, may be used. Theconductive layer may be backed by or integrated into substrates such aspolyethylene terephthalate, polyethylene naphthalate, polyaramid,polyimide, polycycloolefin, polysulfone, epoxy and their composites. Theconductor film may be coated with a radiation curable polymer precursorlayer. The film and precursor layer are then exposed imagewise toradiation to form the microcell wall structure. Following exposure, theprecursor material is removed from the unexposed areas, leaving thecured microcell walls bonded to the conductor film/support web. Theimagewise exposure may be accomplished by UV or other forms of radiationthrough a photomask to produce an image or predetermined pattern ofexposure of the radiation curable material coated on the conductor film.Although it is generally not required, the mask may be positioned andaligned with respect to the conductor film, i.e., ITO lines, so that thetransparent mask portions align with the spaces between ITO lines, andthe opaque mask portions align with the ITO material (intended formicrocell cell floor areas).

Photolithography. Microcells can also be produced usingphotolithography. Photolithographic processes for fabricating amicrocell array are illustrated in FIGS. 6A and 5B. As shown in FIGS. 6Aand 6B, the microcell array 600 may be prepared by exposure of aradiation curable material 601 a coated by known methods onto aconductor electrode film 602 to UV light (or alternatively other formsof radiation, electron beams and the like) through a mask 606 to formwalls 601 b corresponding to the image projected through the mask 606.The base conductor film 602 is preferably mounted on a supportivesubstrate base web 603, which may comprise a plastic material.

In the photomask 606 in FIG. 6A, the dark squares 604 represent theopaque area and the space between the dark squares represents thetransparent area 605 of the mask 606. The UV radiates through thetransparent area 605 onto the radiation curable material 601 a. Theexposure is preferably performed directly onto the radiation curablematerial 601 a, i.e., the UV does not pass through the substrate 603 orbase conductor 602 (top exposure). For this reason, neither thesubstrate 603, nor the conductor 602, needs to be transparent to the UVor other radiation wavelengths employed.

As shown in FIG. 6B, the exposed areas 601 b become hardened and theunexposed areas (protected by the opaque area 604 of the mask 606) arethen removed by an appropriate solvent or developer to form themicrocells 607. The solvent or developer is selected from those commonlyused for dissolving or reducing the viscosity of radiation curablematerials such as methylethylketone (MEK), toluene, acetone, isopropanolor the like. The preparation of the microcells may be similarlyaccomplished by placing a photomask underneath the conductorfilm/substrate support web and in this case the UV light radiatesthrough the photomask from the bottom and the substrate needs to betransparent to radiation.

Imagewise Exposure. Still another alternative method for the preparationof the microcell array of the invention by imagewise exposure isillustrated in FIGS. 6C and 6D. When opaque conductor lines are used,the conductor lines can be used as the photomask for the exposure fromthe bottom. Durable microcell walls are formed by additional exposurefrom the top through a second photomask having opaque linesperpendicular to the conductor lines. FIG. 6C illustrates the use ofboth the top and bottom exposure principles to produce the microcellarray 610 of the invention. The base conductor film 612 is opaque andline-patterned. The radiation curable material 611 a, which is coated onthe base conductor 612 and substrate 613, is exposed from the bottomthrough the conductor line pattern 612, which serves as the firstphotomask. A second exposure is performed from the “top” side throughthe second photomask 616 having a line pattern perpendicular to theconductor lines 612. The spaces 615 between the lines 614 aresubstantially transparent to the UV light. In this process, the wallmaterial 611 b is cured from the bottom up in one lateral orientation,and cured from the top down in the perpendicular direction, joining toform an integral microcell 617. As shown in FIG. 6D, the unexposed areais then removed by a solvent or developer as described above to revealthe microcells 617.

The microcells may be constructed from thermoplastic elastomers, whichhave good compatibility with the microcells and do not interact with themedia. Examples of useful thermoplastic elastomers include ABA, and(AB)n type of di-block, tri-block, and multi-block copolymers wherein Ais styrene, α-methylstyrene, ethylene, propylene or norbornene; B isbutadiene, isoprene, ethylene, propylene, butylene, dimethylsiloxane orpropylene sulfide; and A and B cannot be the same in the formula. Thenumber, n, is ≥1, preferably 1-10. Particularly useful are di-block ortri-block copolymers of styrene or ox-methylstyrene such as SB(poly(styrene-b-butadiene)), SBS (poly(styrene-b-butadiene-b-styrene)),SIS (poly(styrene-b-isoprene-b-styrene)), SEBS(poly(styrene-b-ethylene/butylenes-b-stylene))poly(styrene-b-dimethylsiloxane-b-styrene),poly((α-methylstyrene-b-isoprene),poly(α-methylstyrene-b-isoprene-b-α-methylstyrene),poly(α-methylstyrene-b-propylene sulfide-b-α-methylstyrene),poly(α-methylstyrene-b-dimethylsiloxane-b-α-methylstyrene). Commerciallyavailable styrene block copolymers such as Kraton D and G series (fromKraton Polymer, Houston, Tex.) are particularly useful. Crystallinerubbers such as poly(ethylene-co-propylene-co-5-methylene-2-norbomene)or EPDM (ethylene-propylene-diene terpolymer) rubbers such as Vistalon6505 (from Exxon Mobil, Houston, Tex.) and their grafted copolymers havealso been found very useful.

The thermoplastic elastomers may be dissolved in a solvent or solventmixture, which is immiscible with the carrier in the microcells andexhibits a specific gravity less than that of the carrier. Low surfacetension solvents are preferred for the overcoating composition becauseof their better wetting properties over the microcell walls and thefluid. Solvents or solvent mixtures having a surface tension lower than35 dyne/cm are preferred. A surface tension of lower than 30 dyne/cm ismore preferred. Suitable solvents include alkanes (preferably C₆₋₁₂alkalies such as heptane, octane or Isopar solvents from Exxon ChemicalCompany, nonane, decane and their isomers), cycloalkanes (preferablyC₆₋₁₂ cycloalkanes such as cyclohexane and decalin and the like),alkylbezenes (preferably mono- or di-C₁₋₆ alkyl benzenes such astoluene, xylene and the like), alkyl esters (preferably C₂₋₅ alkylesters such as ethyl acetate, isobutyl acetate and the like) and C₃₋₅alkyl alcohols (such as isopropanol and the like and their isomers).Mixtures of alkylbenzene and alkane are particularly useful.

In addition to polymer additives, the polymer mixtures may also includewetting agents (surfactants). Wetting agents (such as the FC surfactantsfrom 3M Company, Zonyl fluorosurfactants from DuPont, fluoroacrylates,fluoromethacrylates, fluoro-substituted long chain alcohols,perfluoro-substituted long chain carboxylic acids and their derivatives,and Silwet silicone surfactants from OSi, Greenwich, Conn.) may also beincluded in the composition to improve the adhesion of the sealant tothe microcells and provide a more flexible coating process. Otheringredients including crosslinking agents (e.g., bisazides such as4,4′-diazidodiphenylmethane and2,6-di-(4′-azidobenzal)-4-methylcyclohexanone), vulcanizers (e.g.,2-benzothiazolyl disulfide and tetramethy thiuram disulfide),multifunctional monomers or oligomers hexanediol, diacrylates,trimethylolpropane, triacrylate, divinylbenzene, thermal initiators(e.g., dilauroryl peroxide, benzoyl peroxide) and photoinitiators (e.g.,isopropyl thioxanthene (ITX), Irgacure 651 and Irgacure 369 fromCiba-Geigy) are also highly useful to enhance the physico-mechanicalproperties of the sealing layer by crosslinking or polymerizationreactions during or after the overcoating process.

After the microcells are produced, they are filled with appropriatecombinations of benefit agents and carrier. The microcell array 70 maybe prepared by any of the methods described above. As shown incross-section in FIGS. 7A-7D, the microcell walls 71 extend upward fromthe backing layer 73 and conducive layer 72 to form the open cells. Inan embodiment, a conductive layer 72 is formed on or at the backinglayer 73. While FIGS. 7A-7D show the conductive layer 72 is continuousand running above the backing layer 73, it is also possible that theconductive layer 72 is continuous and running below or within thebacking layer 73 or it is interrupted by the microcell walls 71. Priorto filling, the microcell array 70 may be cleaned and sterilized toassure that the benefit agents are not compromised prior to use.

The microcells are next filled with a combination of carrier 74 and thebenefit agent 75. As mentioned above, different microcells may includedifferent benefit agents. in systems for delivering hydrophobic benefitagents, the combination may be based upon a biocompatible oil or someother biocompatible hydrophobic carrier. For example, the combinationmay comprise a vegetable, fruit, or nut oil. In other embodiments,silicone oils may be used. In systems for delivering hydrophilic benefitagents. the combination be based upon water, other aqueous media such asphosphate buffer or polar organic solvents. The combination need not bea liquid, however, as gels, such as hydrogels and other matrices, andsemi-solid materials may be suitable to deliver the benefit agents.

The microcells may be filled using a variety of techniques. In someembodiments, where a large number of neighboring microcells are to befilled with an identical composition, blade coating may be used to fillthe microcells to the depth of the microcell walls 71. In otherembodiments, where a variety of different composition are to be filledin a variety of nearby microcell, inkjet-type; microinjection can beused to fill the microcells. In yet other embodiments, microneedlearrays be used to fill an array of microcells with the correctcompositions. The filling may be done in a one-step or multistepprocess. For example, all of the cells may be partially filled with anamount of carrier. The partially filled microcells are then filled witha composition comprising the carrier and one or more benefit agents tobe delivered.

As shown in FIG. 7C, after filling, the microcells are sealed byapplying a polymer composition 76 comprising metallic material, such asmetal nanoparticles, metal nanowires, or metal nanofibers. In someembodiments, the sealing process may involve exposure to heat, dry hotair, or UV radiation. In most embodiments, the polymer should beinsoluble or have low solubility with the carrier 74 and the benefitagent 75. The polymer composition of the sealing layer 76 can also bebiocompatible and selected to adhere to the sides or tops of themicrocell walls 71. An adhesive can also be used to attach the electrodelayer onto the sealing layer. The adhesive may also be electricallyconductive. A suitable biocompatible adhesive for sealing layer is aphenethylamine mixture, such as described in U.S. patent applicationSer. No. 15/336,841 filed Oct. 30, 2016 and tided “Method for SealingMicrocell Containers with Phenethylamine Mixtures”, which isincorporated herein by reference in its entirety. Accordingly, the finalmicrocell structure is mostly impervious to leaks and able to withstandflexing without delamination or separation of the sealing layer or theelectrode layer.

In alternate embodiments, a variety of individual microcells may befilled with the desired mixture by using iterative photolithography. Theprocess typically includes coating an array of empty microcells with alayer of positively working photoresist, selectively opening a certainnumber of the microcells by image-wise exposing the positivephotoresist, followed by developing the photoresist, filling the openedmicrocells with the desired mixture, and sealing the filled microcellsby a sealing process. These steps may be repeated to create sealedmicrocells filled with other mixtures. This procedure allows for theformation of large sheets of microcells having the desired ratio ofmixtures or concentrations.

After the microcells 70 are filled, the sealed array may be laminatedwith an electrode layer comprising a plurality of electrodes 77. Theelectrode layer may be porous to the benefit agents, preferably bypre-coating the electrode layer 77 with an adhesive layer, which may bea pressure sensitive adhesive, a hot melt adhesive, or a heat, moisture,or radiation curable adhesive. The laminate adhesive may be post-curedby radiation such as UV through the top conducting layer if the latteris transparent to the radiation. In other embodiments, the plurality ofelectrodes may be bonded directly to the sealed array of the microcell.In some embodiments, a biocompatible adhesive is then laminated to theassembly. The biocompatible adhesive will allow benefit agents to passthrough while keeping the device mobile on a user. Suitablebiocompatible adhesives are available from 3M (Minneapolis, Minn.).

Once the delivery system has been constructed, it may be covered with arelease sheet to provide protection. The release sheet may also includeadhesives. The benefit agent delivery system may be flexible. This meansthat it can be folded to a certain extend without breaking, a propertysimilar to a thin rubber sheet. The benefit agent delivery system can bean autonomous system that can be easily transported in a small space,such as a handbag, and only needs electric power, which can be a smallbattery to operate.

In some embodiments, it will not be necessary to provide a conductivelayer and an electrode layer on the opposite sides of the system. Forinstance, as shown in FIG. 8 , the benefit agent delivery system 80 mayinclude a voltage source 81 that is grounded into the surface to whichthe delivery system is attached 82. This may be especially useful fortransdermal delivery of drugs, where the skin's natural conductance issufficient to provide a ground potential. Thus, the metallic materialwill be removed from the sealing layer. It may migrate via the mediumand it may be deposited on the opposite inside surface of the microcellas a metal. This is achieved by application of a voltage to at least oneof the electrodes 77 as shown in FIG. 8 . It is appreciated that theelectrode layer comprises a plurality of electrodes whereby individual“pixel” electrodes can be addressed, e.g., with row-column drivers as inan electro-optic display.

Advanced embodiments of a benefit agent delivery system will includecircuitry to allow the benefit agent delivery system to be activatedwirelessly with a secondary device 92, such as a smart phone or smartwatch. As shown in FIG. 9 , a simple system will allow a user toactivate electronic/digital switch which will cause an electric field toopen an electronic/digital switch 94, which will cause an electric fieldto be delivered, thereby causing the migration of the metallic materialof the sealing layer and creating a porous sealing layer through whichthe benefit agent can be delivered at a desired surface or space andgiving the user a dose of the benefit agents. In another embodiment,i.e., as shown in FIG. 10 , the benefit agent delivery system includes acontroller 104 that independently controls the plurality of theelectrodes of the electrode layer. Controller 104 may also be able toreceive wireless signals from a secondary device 102. The embodiment ofFIG. 10 will allow a user to control, for example, the type of benefitagent that is delivered and the amount at the desired time. Using anapplication on the secondary device 102 it may be possible to programthe benefit agent delivery system to modify the amount of benefit agentbased upon the time of day. In other embodiments, the application may beoperatively connected to biometric sensors, e.g., a fitness tracker,whereby the application causes the dosage to be turned off if, e.g., thepulse rate of the user exceeds a preset threshold.

When driving the benefit agent delivery systems of FIGS. 9 and 10 , NFC,Bluetooth, WIFI, or other wireless communication function is turned on,allowing a user to manipulate the applied voltage across the microcellsin order to activate the desired microcells. The activation can beinitiated before or after the benefit agent delivery system is appliedon the desired surface or location. In addition, benefit agent releaseadjustment can be achieved at any time when necessary. Because themicrocell activation is controlled by smart watch or smart phone, thepercentage and area for all of the microcells at different activationstatus is known, which means all of the usage data will be available toa user or a provider, including the time of the system activation andthe amount of the benefit agent(s) administered. Thus, the system mayprovide a precise control to the user or another person (i.e. a doctoror health provider) to adjust the benefit agent delivery. Because everymicrocell can be activated independently, the system is programmable.That is, the overall benefit agent delivery can be programmed byactivating each of the plurality of microcell when desired. For abenefit agent delivery system, which is designed to deliver benefitagents transdermally, the skin irritation can be mitigated because ofthe benefit agent can be controlled to be released over a period oftime. Additionally, in drug delivery applications, patient compliancecan be done effectively, because the smart device that is used toactivate the system can remotely communicate with the physician for datasharing.

It is to be understood that the invention is not limited to combinationsof benefit agents in the microcell, as different benefit agents can bedelivered by adding those benefit agents to additional layers of thebenefit agent delivery system. FIG. 11 exemplifies a benefit agentdelivery system that comprises in order, a backing layer 110, aconductive layer 120, a plurality of microcells layer 135, a sealinglayer comprising metallic material, an adhesive layer 180, an electrodelayer, and a release sheet 115. As shown in FIG. 11 , the benefit agentsmay be present in, for example, the adhesive layer.

Area A of FIG. 11 exemplified two different benefit agents being loadedinto the plurality of microcell layer 135 and the adhesive layer 180. Insome embodiments, the two benefit agents may be delivered at the sametime. They may also have different delivery profiles. The system alsoprovides a way to deliver different benefit agents with differentphysical properties, such as different hydrophobicities. For example, ifthe carrier of the microcell is polar, a hydrophilic benefit agent canbe loaded into microcell at high loading. In this embodiment, theadhesive layer may include a hydrophobic benefit agent. Accordingly, therelease profile of the two benefit agents can also be adjusted nearlyindependently. This system overcomes the problem of stabilizing abenefit agent with unfavorable solubility with, e.g., surfactants,capsules, etc.

Area B of FIG. 11 illustrates an embodiment in which the same benefitagent is loaded in both the microcells and the adhesive layer 180.Depending on the characteristics of the benefit agent, this method canhelp to load larger quantities of benefit agent into the benefit agentdelivery system, which can help to increase the benefit agent releaseamount and control the release profile.

Area C of FIG. 11 illustrates an embodiment in which a combination ofbenefit agents is loaded either into the microcell, or into the adhesivelayer 180, or into both layers. The benefit agents in the microcellcomposition and adhesive layer can be the same or different. The numberof benefit agents in the microcell formulation and the number of benefitagents in the adhesive layer can also be the same or different.

A benefit agent-loading layer 185 can be included into the benefit agentdelivery system adjacent to the release sheet 115, as shown in FIG. 12 .The amount and types of benefit agents in the benefit agent-loadinglayer 185 can be independent of the loading in the microcells and/or inthe adhesive layer. The benefit agent can be introduced into only someportions of the adhesive layer, or it can present in both adhesive 180and the benefit agent-loading layer 185. The benefit agent-loading layer185 may be porous. In another example, the benefit-loading layer may belocated between the sealing layer 160 and the adhesive layer 180.

The benefit agent delivery system may also comprise a porous diffusionlayer or a rate control layer that is disposed between the sealing layerand the electrode layer. If there is an adhesive layer adjacent to thesealing layer, the porous diffusion layer or the rate control layer maybe disposed between the adhesive layer and the electrode layer. Theporous diffusion layer or the rate control layer and the adhesive layermay be integrated into one layer, which may have volume resistivity ofless than 10⁻¹⁰ Ohm*cm, or less than 10⁻⁹ Ohm*cm. That is, the porousdiffusion layer or the rate control layer may also serve as an adhesivelayer, establishing an adhesive connection between the sealing layer andthe electrode layer. The porous diffusion layer or the rate controllayer and the electrode layer may also be integrated into one layer.

The porous diffusion layer may have average pore size larger than 0.2nm. The rate control layer may have average pore size of 0.2 nm andsmaller. The porous diffusion layer and the rate control layer maycontrol the rate of the delivery of the benefit agent by its porosity,pore size, layer thickness, the chemical structure, and the polarity ofthe material from which it is constructed. Thus, for example, a ratecontrol layer, positioned adjacent to the sealing layer or adjacent tothe electrode layer, and made with a nonpolar polymer such aspolyethylene having some porosity level may reduce the rate of deliveryof relatively polar benefit agents, such as, for example benefit agentsthat are soluble or dispersible in water. In addition, a rate controllayer having low porosity or higher thickness may slow down the deliveryof benefit agents.

As mentioned above, various layers of the benefit agent delivery systemmay be combined or integrated in a single layer. For example, anadhesive layer an adjacent electrode layer may also be integrated intoone layer. The same may be true for the combination of the porousdiffusion layer or the rate control layer and the electrode layer, thecombination of the sealing layer and the benefit agent-loading layer,the combination of the benefit agent-loading layer and the rate controllayer, etc.

In an embodiment, the present invention is a method of operating abenefit agent delivery system. The benefit agent delivery systemcomprises (a) a conductive layer, (b) a plurality of microcells, whereineach microcell includes an opening and contains a carrier and a benefitagent, (c) a sealing layer spanning the opening of each microcell andcomprising a polymeric material and a metallic material, (d) anelectrode layer, and (e) a voltage source. The voltage source is coupledto the conductive layer and the electrode layer. The conductive layer,the microcell layer, the sealing layer and the electrode layer arevertically stacked upon each other. The microcell layer and the sealinglayer are disposed between the conductive layer and the electrode layer.The conductive layer, the microcell layer, the sealing layer and theelectrode layer may be vertically stacked upon each other in this order.Alternatively, the electrode layer, the microcell layer, the sealinglayer and the conductive layer may be vertically stacked upon each otherin this order. The method of operating the benefit agent delivery systemcomprises the steps of: providing the benefit delivery system andapplying a voltage potential difference between the conductive layer andthe electrode layer to generate an electric field; the electric fieldhas a polarity causing the migration of the metallic material onto asurface of the microcell adjacent to the conductive layer. This removalof the metallic material of the sealing layer creates porosity to thesealing layer, enabling the delivery of the benefit agent. The methodfor operating a benefit agent delivery system may further comprise astep of controlling the rate of delivery of the benefit agent by theselection of the applied voltage potential. Higher voltage potentialenables higher rate of release of the benefit agent by increasing therate of removal of the metallic material from the sealing layer,reducing the time of the creation of its porosity.

EXAMPLE On Demand Delivery of a Fragrance

A benefit agent delivery system that can be represented by FIG. 1A wasconstructed. The system comprised in order, a backing layer, aconductive layer, a plurality of microcells, a sealing layer, anadhesive layer, and an electrode layer. The conductive layer comprisedan Indium-Tin oxide combination. The plurality of microcells comprised amedium composition (or internal phase) comprising 20 weight % of methylsalicylate fragrance in 80 weight % of triethyl citrate solvent. Themicrocells were sealed using a polymeric composition comprising 10weight % of silver metal nanofibers by weight of the sealing layer. Thesilver nanofibers have an average diameter of 40 nm and an averagelength of 15 μm. FIG. 13 is a microphotograph of the sealing layercomprising the silver nanofibers, acquired after the microcells weresealed. A porous electrode layer comprising a plurality of electrodeswas first coated with an adhesive composition, and laminated on thesealing layer. The conductive layer was electrically connected to theelectrode layer and a voltage source. A voltage of 40 V was applied for4 minutes on the left half part of the benefit agent delivery system.The voltage was applied so that the electrode layer was the anode(positive polarity) and the conductive layer was the cathode (negativepolarity). Seven panelists evaluated the system by smelling the systemfrom a distance of 30 cm before and after the application of thevoltage. They ranked the benefit agent delivery system by using a fourpoint scale, as follows:

-   -   3: A strong fragrance odor was sensed after the activation in        comparison to the odor before the activation.    -   2: A moderate fragrance odor was sensed after the activation in        comparison to the odor before the activation.    -   1: Very slight fragrance odor was sensed after the activation in        comparison to the odor before the activation.    -   0: No difference in odor was sensed after the activation in        comparison to the odor before the activation.        The average score for the seven panelist was 2.6. Thus, the        panelists sensed that there was a significant odor of the        fragrance after the activation of the system in comparison to        the odor before the activation.

Photographic images of the constructed benefit agent delivery systemwere acquired from the side of the backing layer before (FIG. 14A) andafter (FIG. 14B) the application of the electric field. In FIG. 14B,only the left side of the delivery system was activated. No voltage wasapplied on the right part of the delivery system. Both the image of FIG.14A and the right side of the image of FIG. 14B, show that that thebacking layer has a light yellow color. On the contrary, the left partof FIG. 14B, corresponding to the part of the system that was activated,is dark gold. The darker color was attributed to a metallic silver layerdeposited on the inside surface of the microcells adjacent to theconductive layer of the activated microcells. This is evidence that thesilver nanofibers, which were present in the sealing layer before theactivation, migrated from the sealing layer and deposited as metalliclayer near the cathode.

FIGS. 15A and 15B are microphotographs of the non-activated andactivated microcells, respectively. More specifically, after theapplication of the voltage at the benefit agent delivery system asdescribed above, the sealing layer was removed and microphotographs ofthe microcell layer were acquired looking from the opening of themicrocells. The image of FIG. 15A corresponds to the inside surface ofthe non-activated microcells and the image of FIG. 15B corresponds tothe inside surface of the activated microcells. The hexagonal shape ofthe microcells in the case of the non-activated portion is barelyvisible. On the contrary, the hexagonal shape of the microcells in thecase of the activated portion is distinctly visible, because thedeposition of the silver on the surface of the microcells increases thecontrast between the surface of the microcell adjacent to the conductivelayer and the walls of the microcells. This is another strong indicationthat the silver nanofibers, which were present in the sealing layerbefore the activation, migrated from the sealing layer and deposited onthe inside surface of the microcells adjacent to the conductive layer.This process created a porous sealing layer through which the fragrancematerial was delivered in the vicinity of the benefit agent deliverysystem and was detected as fragrance odor by the panelists.

Thus, the invention provides for a benefit agent delivery systemincluding a plurality of microcells, which include a carrier and abenefit agent, and a sealing layer comprising a metallic material in apolymer. Application of a voltage on the system results in the migrationof the metallic material of the sealing and the creation of a poroussealing layer. The porosity of the sealing layer permits for the benefitagent to be delivered from the benefit agent delivery system. Thisdisclosure is not limiting, and other modifications to the invention,not described, but self-evident to one of skill in the art, are to beincluded in the scope of the invention.

The invention claimed is:
 1. A method for operating a benefit agentdelivery system comprising the steps of: providing a benefit agentdelivery system comprising (a) a conductive layer, (b) a plurality ofmicrocells, each microcell including an opening and containing a carrierand a benefit agent, (c) a sealing layer spanning the opening of eachmicrocell and comprising a polymeric material and a metallic material,(d) an electrode layer; and (e) a voltage source; wherein the conductivelayer, the microcell layer, the sealing layer and the electrode layerare vertically stacked upon each other; wherein the microcell layer andthe sealing layer are disposed between the conductive layer and theelectrode layer; and wherein the voltage source is coupled to theconductive layer and the electrode layer; applying a voltage potentialdifference between the conductive layer and the electrode layer togenerate an electric field having a polarity causing the migration ofthe metallic material onto a surface of the microcell adjacent to theconductive layer.
 2. The method for operating a benefit agent deliverysystem according to claim 1, further comprising a step of controllingthe rate of delivery of the benefit agent by the selection of theapplied voltage potential.
 3. The method for operating a benefit agentdelivery system according to claim 1, wherein, when a voltage is appliedfrom a voltage source between the conductive layer and the electrodelayer, the metallic material is removed from the sealing layer, creatinga porous sealing layer.
 4. The method for operating a benefit agentdelivery system according to claim 1, wherein the conductive layer, themicrocell layer, the sealing layer and the electrode layer arevertically stacked upon each other in this order, and wherein theelectrode layer is porous.
 5. The method for operating a benefit agentdelivery system according to claim 1, wherein the polymeric material ofthe sealing layer is selected from the group consisting of an acrylate,a methacrylate, a polycarbonate, a polyvinyl alcohol, cellulose,poly(N-isopropylacrylamide) (PNIPAAm), poly(lactic-co-glycolic acid)(PLGA), polyvinylidene chloride, acrylonitrile, amorphous nylon,oriented polyester, terephthalate, polyvinyl chloride, polyethylene,polypropylene, polystyrene, polyurethane, and alginate.
 6. The methodfor operating a benefit agent delivery system according to claim 1,wherein the metallic material of the sealing layer is selected from thegroup consisting of metal particles, metal wires, metal fibers, metalflakes, metal rods, metal aggregates, and metal disks.
 7. The method foroperating a benefit agent delivery system according to claim 1, whereinthe metallic material of the sealing layer comprises silver, copper,gold, platinum, zinc, chromium, nickel or combination thereof
 8. Themethod for operating a benefit agent delivery system according to claim1, wherein the sealing layer further comprises a conductive materialselected from the groups consisting of carbon black, carbon nanotubes,graphene, a dopant, and a conductive polymer.
 9. The method foroperating a benefit agent delivery system according to claim 1, whereinthe carrier is selected from the group consisting of a liquid, asemi-solid, a gel and combinations thereof
 10. The method for operatinga benefit agent delivery system according to claim 1, wherein thecarrier is selected from a group comprising water, an organic compound,a silicone compound, and a combination thereof
 11. The method foroperating a benefit agent delivery system according to claim 1, whereinthe plurality of microcells comprises a benefit agent selected from thegroup consisting of a pharmaceutical agent, a vaccine, an antibody, ahormone, a protein, a nucleic acid, a nutraceutical agent, a nutrient, acosmetic agent, a fragrance, a malodor removing agent, an agriculturalagent, an air care agent, an anti-microbial agent, and a preservative.12. The method for operating a benefit agent delivery system accordingto claim 1, wherein the sealing layer further comprises a benefit agent.13. The method for operating a benefit agent delivery system accordingto claim 1, wherein the sealing layer and the electrode layer areintegrated into one layer.
 14. The method for operating a benefit agentdelivery system according to claim 4, further comprising a porousdiffusion layer or a rate control layer between the sealing layer andthe electrode layer.
 15. The method for operating a benefit agentdelivery system according to claim 14, wherein the electrode layer andthe porous diffusion layer are integrated into one layer.
 16. The methodfor operating a benefit agent delivery system according to claim 4,further comprising an adhesive layer disposed between the sealing layerand the electrode layer.
 17. The method for operating a benefit agentdelivery system according to claim 16, further comprising a porousdiffusion layer disposed between the adhesive layer and the electrodelayer.
 18. The method for operating a benefit agent delivery systemaccording to claim 17, wherein the porous diffusion layer and theadhesive layer is integrated in one layer, and wherein the integratedlayer has volume resistivity of less than 10⁻¹⁰ Ohm cm.